Biological Trace Element Research

, Volume 56, Issue 1, pp 63–91 | Cite as

Genomic structures of viral agents in relation to the biosynthesis of selenoproteins

  • Ethan Will Taylor
  • Ram Gopal Nadimpalli
  • Chandra Sekar Ramanathan


The genomes of both bacteria and eukaryotic organisms are known to encode selenoproteins, using the UGA codon for selenocysteine (SeC), and a complex cotranslational mechanism for SeC incorporation into polypeptide chains, involving RNA stem-loop structures. These common features and similar codon usage strongly suggest that this is an ancient evolutionary development. However, the possibility that some viruses might also encode selenoproteins remained unexplored until recently. Based on an analysis of the genomic structure of the human immunodeficiency virus HIV-1, we demonstrated that several regions overlapping known HIV genes have the potential to encode selenoproteins (Taylor et al.[31], J. Med. Chem.37, 2637–2654 [1994]). This is provocative in the light of over-whelming evidence of a role for oxidative stress in AIDS pathogenesis, and the fact that a number of viral diseases have been linked to selenium (Se) deficiency, either in humans or by in vitro and animal studies. These include HIV-AIDS, hepatitis B linked to liver disease and cancer, Coxsackie virus B3, Keshan disease, and the mouse mammary tumor virus (MMTV), against which Se is a potent chemoprotective agent. There are also established biochemical mechanisms whereby extreme Se deficiency can induce a proclotting or hemorrhagic effect, suggesting that hemorrhagic fever viruses should also be examined for potential virally encoded selenoproteins. In addition to the RNA stem-loop structures required for SeC insertion at UGA codons, genomic structural features that may be required for selenoprotein synthesis can also include ribosomal frameshift sites and RNA pseudoknots if the potential selenoprotein module overlaps with another gene, which may prove to be the rule rather than the exception in viruses. One such pseudoknot that we predicted in HIV-1 has now been verified experimentally; a similar structure can be demonstrated in precisely the same location in the reverse transcriptase coding region of hepatitis B virus. Significant new findings reported here include the existence of highly distinctive glutathione peroxidase (GSH-Px)-related sequences in Coxsackie B viruses, new theoretical data related to a previously proposed potential selenoprotein gene overlapping the HIV protease coding region, and further evidence in support of a novel frameshift site in the HIVnef gene associated with a well-conserved UGA codon in the-1 reading frame.

Index Entries

AIDS genomic analysis glutathione peroxidase HIV retrovirus RNA viruses selenium selenoproteins 


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  1. 1.
    S. Y. Yu, W. G. Li, Y. J. Zhu, W. P. Yu, and C. Hou,Biol. Trace Element Res. 20, 15–22 (1989).Google Scholar
  2. 2.
    S. Y. Yu, Y. J. Zhu, W. G. Li, Q. S. Huang, C. Z. Huang, Q. N. Zhang and C. Hou,Biol. Trace Element Res. 29, 289–294 (1991).CrossRefGoogle Scholar
  3. 3.
    J. Bai, S. Wu, K. Ge, X. Deng and C. Su,Acta Acad. Med. Sin. 2, 29–31 (1980).Google Scholar
  4. 4.
    M. A. Beck, P. C. Kolbeck, L. H. Rohr, Q. Shi, V. C. Morris and O. A. Levander,J. Med. Virol. 43, 166–170 (1994).PubMedCrossRefGoogle Scholar
  5. 5.
    J. C. Hou, Z. Y. Jiang and Z. F. He,Chung Hua I Hsueh Tsa Chih 73, 645–646 (1993).PubMedGoogle Scholar
  6. 6.
    G. N. Schrauzer, T. Molenaar, K. Kuehn and D. Waller,Biol. Trace Element Res. 20, 169–178 (1989).Google Scholar
  7. 7.
    B. M. Dworkin, G. P. Wormser, W. S. Rosenthal, S. K. Heier, M. Braunstein, L. Weiss, R. Jankowski, D. Levy and S. Weiselberg,Am. J. Gastroenterol. 80, 774 (1985).PubMedGoogle Scholar
  8. 8.
    B. M. Dworkin, W. S. Rosenthal, G. P. Wormser and L. Weiss,J. Parenter. Enteral Nutr. 10, 405–407 (1986).Google Scholar
  9. 9.
    J. F. Zazzo, J. Chalas, A. Lafont, F. Camus and P. Chappuis,J. Parenter. Enteral Nutr. 12, 537–538 (1988).Google Scholar
  10. 10.
    B. M. Dworkin, W. S. Rosenthal, G. P. Wormser, L. Weiss, M. Nunez, C. Joline and A. Herp,Biol. Trace Element Res. 15, 167–177 (1988).CrossRefGoogle Scholar
  11. 11.
    B. M. Dworkin, P. P. Antonecchia, F. Smith, L. Weiss, M. Davidian, D. Rubin and W. S. Rosenthal,J. Parenter. Enteral Nutr. 13, 644–647 (1989).Google Scholar
  12. 12.
    L. Olmsted, G. N. Schrauzer, M. Flores-Arce and J. Dowd,Biol. Trace Element Res. 20, 59–65 (1989).Google Scholar
  13. 13.
    K. W. Beck, P. Schramel, A. Held, H. Jaeger and W. Kaboth,Biol. Trace Element Res. 25, 89–96 (1990).Google Scholar
  14. 14.
    A. L. Kavanaugh-McHugh, A. Ruff, E. Perlman, N. Hutton, J. Modlin and S. Rowe,J. Parenter. Enteral Nutr. 15, 347–351 (1991).Google Scholar
  15. 15.
    A. Cirelli, M. Ciardi, C. de-Simone, F. Sorice, R. Giordano, L. Ciaralli and S. Costantini,Clin. Biochem. 24, 211–214 (1991).PubMedCrossRefGoogle Scholar
  16. 16.
    C. Allavena, B. Dousset, T. May, C. Amiel, F. Nabet-Belleville and P. Canton,Presse. Med. 20, 1737 (1991).PubMedGoogle Scholar
  17. 17.
    E. Mantero-Atienza, R. S. Beach, M. C. Gavancho, R. Morgan, G. Shor-Posner and M. K. Fordyce-Baum,J. Parenter. Enteral Nutr. 15, 693–694 (1991).Google Scholar
  18. 18.
    J. P. Revillard, C. M. Vincent, A. E. Favier, M. J. Richard, M. Zittoun and M. D. Kazatchkine,J. Acquired Immune Defic. Syndr. 5, 637–638 (1992).Google Scholar
  19. 19.
    J. Constans, J. L. Pellegrin, E. Peuchant, M. F. Thomas, M. F. Dumon, C. Sergeant and M. Simonoff,Rev. Med. Interne. 14, 1003 (1993).PubMedGoogle Scholar
  20. 20.
    A. Favier, C. Sappey, P. Leclerc, P. Faure and M. Micoud,Chem.-Biol. Interact. 91, 165–180 (1994).PubMedCrossRefGoogle Scholar
  21. 21.
    B. M. Dworkin,Chem.-Biol. Interact. 91, 181–186 (1994).PubMedCrossRefGoogle Scholar
  22. 22.
    R. Bologna, F. Indacochea, G. Shor-Posner, E. Mantero-Atienza, M. Grazziutti, M.-C. Sotomayor, M. Fletcher, C. Cabrejos, G. B. Scott and M. K. Baum.J. Nutr. Immunol. 3, 41–49 (1994).CrossRefGoogle Scholar
  23. 23.
    C. Sergeant, M. Simonoff, C. Hamon, E. Peuchant, M. F. Dumon, M. Clerc, M. J. Thomas, J. Constant, C. Conri, J. L. Pellegrin and B. Leng, inOxidative Stress, Cell Activation and Viral Infection C. Pasquier, ed., Birkhauser Verlag, Basel, pp. 341–351 (1994).Google Scholar
  24. 24.
    G. N. Schrauzer and J. Sacher,Chem.-Biol. Interact. 91, 199–206 (1994).PubMedCrossRefGoogle Scholar
  25. 25.
    C. Allavena, B. Dousset, T. May, F. Dubois, P. Canton and F. Belleville,Biol. Trace Element Res. 47, 133–138 (1995).CrossRefGoogle Scholar
  26. 26.
    C. Sappey, S. Legrand-Poels, M. Best-Belpomme, A. Favier, B. Rentier and J. Piette,AIDS Res. Human Retroviruses 10, 1451–1461 (1994).Google Scholar
  27. 27.
    M. A. Beck, Q. Shi, V. C. Morris and O. A. Levander,Nature Med. 1, 433–436 (1995).PubMedCrossRefGoogle Scholar
  28. 28.
    A. Bock, K. Forchhammer, J. Heider, W. Leinfelder, G. Sawers, B. Veprek and F. Zinoni,Mol. Microbiol. 5, 515–20 (1991).PubMedCrossRefGoogle Scholar
  29. 29.
    M. J. Berry and P. R. Larsen,Biochem. Soc. Trans. 21, 827–832 (1993).PubMedGoogle Scholar
  30. 30.
    B. K. Rima,Biochem. Soc. Trans. 1, 1–13 (1996).Google Scholar
  31. 31.
    E. W. Taylor, C. S. Ramanathan, R. K. Jalluri and R. G. Nadimpalli,J. Med. Chem. 37, 2637–2654 (1994).PubMedCrossRefGoogle Scholar
  32. 32.
    E. W. Taylor, C. S. Ramanathan and R. G. Nadimpalli, in M. Witten, ed.,Computational Medicine, Public Health and Biotechnology: Building a Man in the Machine Part 1, World Scientific, London, pp. 285–309 (1996).Google Scholar
  33. 33.
    A. Sanchez, S. G. Trappier, B. W. J. Mahy, C. J. Peters and S. T. Nichol,Proc. Natl. Acad. Sci. USA 93, 3602–3607 (1996).PubMedCrossRefGoogle Scholar
  34. 34.
    D. L. Hatfield, J. G. Levin, A. Rein and S. Oroszlan,Adv. Virus Res. 41, 193–239 (1992).PubMedGoogle Scholar
  35. 35.
    T. Jacks, M. D. Power, F. R. Masiarz, P. A. Luciw, P. J. Barr and H. E. Varmus,Nature 331, 280–283 (1988).PubMedCrossRefGoogle Scholar
  36. 36.
    T. G. Parslow, inHuman Retroviruses, B. R. Cullen, ed., Oxford University Press, New York, pp. 101–136, (1993).Google Scholar
  37. 37.
    T. Jacks, H. D. Madhani, F. R. Masiarz and H. E. Varmus,Cell 55, 447–458 (1988).PubMedCrossRefGoogle Scholar
  38. 38.
    I. Brierley and J. A. Jenner,J. Mol. Biol. 227, 463–479 (1992).PubMedCrossRefGoogle Scholar
  39. 39.
    R. B. Weiss,Current Opin. Cell Biol. 3, 1051–1055 (1991).CrossRefGoogle Scholar
  40. 40.
    M. Chammoro, N. Parkin and H. E. Varmus,Proc. Natl. Acad. Sci. USA 89, 713–717 (1992).CrossRefGoogle Scholar
  41. 41.
    E. ten Dam, K. Pleij and D. Draper,Biochemistry 31, 11,665–11,676 (1992).Google Scholar
  42. 42.
    J. Gallant and D. Lindsley,Biochem. Soc. Trans. 21, 817–821 (1993).PubMedGoogle Scholar
  43. 43.
    M. H. de Smit, J. van Duin, P. H. van Knippenberg and G. H. van Eijk,Gene 143, 43–47 (1994).PubMedCrossRefGoogle Scholar
  44. 44.
    Q. Shen, F. F. Chu and P. E. Newburger,J. Biol. Chem. 268, 11463–9 (1993).PubMedGoogle Scholar
  45. 45.
    M. J. Berry, L. Banu, J. W. Harney and P. R. Larsen,EMBO J. 12, 3315–3322 (1993).PubMedGoogle Scholar
  46. 46.
    J.-M. A. Battigello, M. Cui, S. Roshong and B. Carter,Bioorganic Med. Chem. 3, 839–849 (1995).CrossRefGoogle Scholar
  47. 47.
    E. W. Taylor, C. S. Ramanathan, R. G. Nadimpalli, and R. F. Schinazi,Antiviral Res. 26, A271, #86 (1995).Google Scholar
  48. 48.
    T. G. Senkevich, J. J. Bugert, J. R. Sisler, E. V. Koonin, G. Darai, and B. Moss,Science 273, 813–816 (1996).PubMedCrossRefGoogle Scholar
  49. 49.
    R. G. Nadimpalli, J. A. Hamilton, A. Thakur, R. G. Dean, E. W. Taylor, and B. M. Blumberg,Virus Res., submitted for publication (1997).Google Scholar
  50. 50.
    J. Engel,FEBS Lett. 251, 1–7 (1989).PubMedCrossRefGoogle Scholar
  51. 51.
    A. Opgenorth, N. Nation, K. Graham and G. McFadden,Virology 192, 701–709 (1993).PubMedCrossRefGoogle Scholar
  52. 52.
    T. M. Buttke and P. A. Sandstrom,Free Radical Res. 22, 389–397 (1994).Google Scholar
  53. 53.
    Z. Du, D. P. Giedroc and D. W. Hoffman,Biochemistry 35, 4187–4198 (1996).PubMedCrossRefGoogle Scholar
  54. 54.
    Y. Wang, J. F. Holland, I. J. Bleiweiss, S. Melana, X. Liu, I. Pelisson, A. Cantarella, K. Stellrecht, S. Mani, and B. G.-T. Pogo,Cancer Res. 55, 5173–5179 (1995).PubMedGoogle Scholar
  55. 55.
    C. S. Ramanathan and E. W. Taylor, Computational genomic analysis of hemorrhagic fever viruses.Biol. Trace Element Res. 56, 93–106 (1997).Google Scholar
  56. 56.
    F. Wong-Staal, R. C. Gallo, N. T. Chang, J. Ghrayeb, T. S. Papas, J. A. Lautenberger, M. L. Pearson, S. R. Petteway Jr., L. Ivanoff, K. Baumeister, E. A. Whitehorn, J. A. Rafalski, E. R. Doran, S. J. Joseph, B. Starcich, K. J. Livak, R. Patarca, W. A. Haseltine, and L. Ratner, Complete nucleotide sequence of the aids virus, htlv-iii,Nature 313, 277–284 (1985).CrossRefGoogle Scholar
  57. 57.
    G. N. Schrauzer, D. A. White and C. J. Schneider,Bioinorg. Chem. 6, 265–270 (1976).PubMedCrossRefGoogle Scholar

Copyright information

© Humana Press Inc. 1997

Authors and Affiliations

  • Ethan Will Taylor
    • 1
    • 2
  • Ram Gopal Nadimpalli
    • 1
    • 2
  • Chandra Sekar Ramanathan
    • 1
    • 2
  1. 1.Computational Center for Molecular Structure and DesignThe University of GeorgiaAthens
  2. 2.Department of Medicinal ChemistryThe University of GeorgiaAthens

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